Journal
EUROPEAN JOURNAL OF NEUROLOGY
Volume 29, Issue 12, Pages 3737-3741Publisher
WILEY
DOI: 10.1111/ene.15512
Keywords
genetics; Parkinson's disease; PLXNA1; rare variant
Categories
Funding
- National Key Research and Development Program of China [2021YFC2501200]
- Sichuan Science and Technology Program [2022ZDZX0023, 2021YJ0415]
- National Natural Science Foundation of China [81901294, 81871000]
Ask authors/readers for more resources
A potential cause of parkinsonism, p.Glu1121Ter in PLXNA1, was identified recently. However, no further replication has been conducted in a wider range of Parkinson's disease (PD) cohorts. Our study evaluated the genetic role of PLXNA1 in PD by analyzing rare protein-coding variants in patients and healthy controls, finding enrichment of ultra-rare variants of PLXNA1 in PD and observing worsened motor symptoms in patients carrying specific variants.
Background and purpose Recently, p.Glu1121Ter in PLXNA1 was identified as a potential cause of parkinsonism. However, no further replication has been conducted in a wider range of Parkinson's disease (PD) cohorts. We aimed to evaluate the genetic role of PLXNA1 in PD. Methods We systematically analyzed the rare protein-coding variants (minor allele frequency [MAF] < 0.01) in 1080 patients and 1051 healthy controls. Fisher's exact test was used to analyze the associations between each variant and risk of PD, while, at gene level, over-representation of rare variants in patients was examined using the optimized sequence kernel association test (SKAT-O). Results In total, 43 rare variants were identified in PD. No variant was significantly associated with risk of PD. Burden analysis showed enrichment of ultra-rare variants (MAF < 0.001) of PLXNA1 in PD. One patient carried a variant (p.E1121D) in the same amino acid as that in the original study. Both patients showed worsened motor symptoms, and developed dyskinesia during follow-up. Conclusions Our study explored the rare variant of PLXNA1 in PD, and paves the way for future research on the genetic role of PLXNA1 in PD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available